Long-distance eye-brain connections, partial vision restored for first time ever in a mammal

The retina, a thin sheet of cells no more than half as thick as a credit card, is the light-sensing part of the eye. If nerve cells were offices, this tiny patch of tissue would be Manhattan.

Imagine all the phone connections between Manhattan and the rest of the world were severed and you had to reconnect them from scratch. That's essentially what's been achieved in a new study published in Nature Neuroscience.

Light-sensing cells in the back of the retina send electrically coded information to other cells in the retina called retinal ganglion cells, which connect the eye to the brain via the optic nerve. Long, electric-wire-like cables, called axons, extend from the ganglion cells in a bundle down the optic nerve and then fan out to numerous regions of the brain, where they hook up with other nerve cells to inform them about the visual world.

“More than a third of the human brain is dedicated to the processing of visual information,” Stanford neuroscientist Andy Huberman, PhD, told me when I interviewed him for a news release on the study, which he carried out in collaboration with researchers from the University of California-San Diego, Harvard Medical School, and the University of Utah.

“Over two dozen brain areas get direct signals from retinal ganglion cells," Huberman said. "Somehow the brain can interpret these electrical signals to say, ‘Wow, that’s a fast-moving car coming my way - I’d better get back on the sidewalk.’”

The retina is actually part of the brain. And virtually no axons in the brain of a mammal such as a mouse or a human, once damaged, ever regenerate on their own (the only known exception being olfactory sensory nerve cells).

In the study, adult mice whose optic nerve in one eye had been crushed received either a regimen of intensive daily exposure to high-contrast visual stimulation (constant images of a moving black-and-white grid), or biochemical manipulations that kicked a growth-enhancing cascade of molecular interactions (the "mTOR pathway") within their retinal ganglion cells back into high gear, or both.

Three weeks later, the "both" group had recovered their ability to respond to visual stimuli. From our release:

One test ... involved the projection of an expanding dark circle — analogous to a bird of prey’s approach —onto the visual field of the damaged eye. In response, most of the mice subjected to both mTOR-pathway upregulation and visual stimulation, as well as obstruction of their remaining good eye, did what they would be expected to do in the wild: They headed for the shelter of a 'safety zone' in the experimental set-up.

On examination, substantial numbers of axons emanating from these mice's retinal ganglion cells had grown back through the optic nerve and found their way to their appropriate target destinations in the brain.

Still, the restoration of vision was incomplete. The mice weren't so good on tests requiring finer-detail perception. Still, this marks the first time any eye-brain connections have ever been restored in a mammal — a step millions of people suffering from serious vision loss will be happy to hear about.

The scenario many of us learned in school is that two X chromosomes make someone female, and an X and a Y chromosome make someone male. These are simplistic ways of thinking about what is scientifically very complex.